Vaishnav, MS and Kumari, N and Srikanta, S and Simha, V and Krishnaswamy, PR and Balaram, P and Bhat, N (2024) Albumin Oxidation and Albumin Glycation Discordance During Type 2 Diabetes Therapy: Biological and Clinical Implications. In: Metabolic Syndrome and Related Disorders, 22 (5). pp. 374-384.
Full text not available from this repository. (Request a copy)Abstract
Aims: Cys34 albumin redox modifications (reversible �cysteinylation� and irreversible �di/trioxidation�), besides being just oxidative stress biomarkers, may have primary pathogenetic roles to initiate and/or aggravate cell, tissue, and vascular damage in diabetes. In an exploratory �proof-of-concept� pilot study, we examined longitudinal changes in albumin oxidation during diabetes therapy. Methods: Mass spectrometric analysis was utilized to monitor changes in human serum albumin (HSA) post-translational modifications glycation glycated albumin (GA), cysteinylation cysteinylated albumin (CA) or human non-mercaptalbumin-1; reversible, di/trioxidation (di/trioxidized albumin or human non-mercaptalbumin-2; irreversible), and truncation (truncated albumin) during ongoing therapy. Four informative groups of subjects were evaluated type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity, and healthy controls at baseline, and subjects with diabetes were followed for a period up to 280 days. Results: At baseline, T2DM was associated with relatively enhanced albumin cysteinylation (CA% total) compared with T1DM (P = 0.004), despite comparable mean hyperglycemia (P values: hemoglobin A1c = 0.09; GA = 0.09). T2DM, compared with T1DM, exhibited selectively and significantly higher elevations of all the �individual� glycated cum cysteinylated (�multimodified�) albumin isoforms (P values: CysHSA+1G = 0.003; CysHSA+2G = 0.007; and CysHSA+3G = 0.001). Improvements in glycemic control and decreases in albumin glycation during diabetes therapy in T2DM were not always associated with concurrent reductions of albumin cysteinylation, and in some therapeutic situations, albumin cysteinylation worsened (glycation-cysteinylation discordance). Important differences were observed between the effects of sulfonylureas and metformin on albumin molecular modifications. Conclusions: T2DM was associated with higher oxidative (cysteinylation) and combined (cysteinylation plus glycation) albumin molecular modifications, which are not ameliorated by improved glucose control alone. Further studies are required to establish the clinical significance and optimal therapeutic strategies to address oxidative protein damage and resulting consequences in diabetes. Copyright 2024, Mary Ann Liebert, Inc., publishers.
| Item Type: | Journal Article |
|---|---|
| Publication: | Metabolic Syndrome and Related Disorders |
| Publisher: | Mary Ann Liebert Inc. |
| Additional Information: | The copyright for this article belongs to Mary Ann Liebert Inc. |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit Division of Interdisciplinary Sciences > Centre for Nano Science and Engineering |
| Date Deposited: | 05 Aug 2024 05:48 |
| Last Modified: | 05 Aug 2024 05:48 |
| URI: | http://eprints.iisc.ac.in/id/eprint/85027 |
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